Infants can access Ebola vaccines during outbreaks
Authors: Mosoka P Fallah, Elizabeth Gonese, Senga Sembuche, Nicaise Ndembi
Journal: The Lancet Global Health (2023)

Historically, there has been a reluctance to conduct clinical research and vaccine trials in children due to their unique vulnerabilities and ethical issues. Since the safety and immunogenicity of a new vaccine are not clearly defined, researchers are cautious when enrolling this vulnerable group.1Laventhal N Tarini BA Lantos J Ethical issues in neonatal and pediatric clinical trials.Pediatr Clin North Am. 2012; 59: 1205-1220Summary Full Text Full Text PDF PubMed Scopus (50) Google Scholar The study by Edward Man-Lik Choi and colleagues2Choi EM-L Lacarra B Afolabi MO et al.Safety and immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in infants: a phase 2, randomised, double-blind, active-controlled trial in Guinea and Sierra Leone.Lancet Glob Health. 2023; 11: e1743-e1752Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar in The Lancet Global Health enriches the literature on the study designs and demonstrates that clinical trials can be safely and effectively done among children without compromising the ethics and integrity of the research.3Joseph PD Craig JC Caldwell PH Clinical trials in children.Br J Clin Pharmacol. 2015; 79: 357-369Crossref PubMed Scopus (210) Google Scholar By conducting the study in two countries, Sierra Leone and Guinea, Choi and colleagues2Choi EM-L Lacarra B Afolabi MO et al.Safety and immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in infants: a phase 2, randomised, double-blind, active-controlled trial in Guinea and Sierra Leone.Lancet Glob Health. 2023; 11: e1743-e1752Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar demonstrated the feasibility of conducting a phase 2 trial and tracking adverse and severe adverse events among infants aged 4–11 months. The researchers achieved a remarkable feat by surmounting the complexities of working with parents and guardians to enrol their infants in a randomised controlled vaccine trial across two countries. In our earlier study,4Fallah MP Reilly C Van Ryn C et al.Pregnancy, pregnancy outcomes, and infant growth and development after recovery from Ebola virus disease in Liberia: an observational cohort study.Lancet Glob Health. 2023; 11: e1053-e1060Summary Full Text Full Text PDF PubMed Scopus (2) Google Scholar we conducted a cohort study in Liberia among women who are pregnant and their neonates and infants to demonstrate that survivors of Ebola who are pregnant or lactating could not transmit the Ebola virus in utero or via breastfeeding to their offspring. However, unlike the trial by Choi and colleagues,2Choi EM-L Lacarra B Afolabi MO et al.Safety and immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in infants: a phase 2, randomised, double-blind, active-controlled trial in Guinea and Sierra Leone.Lancet Glob Health. 2023; 11: e1743-e1752Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar our studies did not introduce an investigational new drug. The successful implementation of the trial by Choi and colleagues2Choi EM-L Lacarra B Afolabi MO et al.Safety and immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in infants: a phase 2, randomised, double-blind, active-controlled trial in Guinea and Sierra Leone.Lancet Glob Health. 2023; 11: e1743-e1752Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar was based on effective social mobilisation and community engagement with the parents. The researchers recruited their desired number of participants within a record 4 months. Building a community of trust with parents and guardians is important for the inclusion of infants in all vaccine research.5Jalloh MF Wilhelm E Abad N Prybylski D Mobilize to vaccinate: lessons learned from social mobilization for immunization in low and middle-income countries.Hum Vaccin Immunother. 2020; 16: 1208-1214Crossref PubMed Scopus (21) Google Scholar The PREVAIL Ebola vaccine trial in Liberia demonstrated the effect of social mobilisation and community engagement in clinical trials during outbreaks when time efficiency is crucial. Social mobilisation and community engagement were shown to ensure a high retention rate and follow-up in clinical trials. In addition to a strong social mobilisation that builds trust with parents, the enrolment of children in the trial by Choi and colleagues2Choi EM-L Lacarra B Afolabi MO et al.Safety and immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in infants: a phase 2, randomised, double-blind, active-controlled trial in Guinea and Sierra Leone.Lancet Glob Health. 2023; 11: e1743-e1752Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar was further precipitated by the fact that there were direct clinical benefits to the control group. The participants in the control group were given WHO-prequalified meningococcal group A, C, W135, and Y conjugate vaccine (MenACWY) instead of a placebo. Although the trial demonstrated the feasibility, safety, and immunogenicity of the Ebola Zaire vaccine among infants younger than 1 year,2Choi EM-L Lacarra B Afolabi MO et al.Safety and immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in infants: a phase 2, randomised, double-blind, active-controlled trial in Guinea and Sierra Leone.Lancet Glob Health. 2023; 11: e1743-e1752Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar a few unanswered questions need to be addressed by future studies. There are variations in the post-vaccination antibody geometric mean concentration (GMC) between participants in the rural setting in Sierra Leone compared with those in the urban setting in Guinea, which warrants further investigation. Researchers need to demonstrate the possibility that the modifying effects of environmental or other biological factors between rural and urban settings could affect vaccine efficacy and effectiveness. This phenomenon was shown in a study conducted by Kabagenyi and collegues7Kabagenyi J Natukunda A Nassuuna J et al.Urban-rural differences in immune responses to mycobacterial and tetanus vaccine antigens in a tropical setting: a role for helminths?.Parasitol Int. 2020; 78102132Crossref PubMed Scopus (11) Google Scholar in 2020 in Uganda, where they compared the immune response to mycobacterial and tetanus vaccine antigens in urban (Entebbe) and rural (Lake Victoria Koome islands) settings in infants and teens (ages 1–17 years). They observed a lower immune response to the antigen in the rural participants than in urban participants. The immune responses were influenced by the helminth burden and other factors.7Kabagenyi J Natukunda A Nassuuna J et al.Urban-rural differences in immune responses to mycobacterial and tetanus vaccine antigens in a tropical setting: a role for helminths?.Parasitol Int. 2020; 78102132Crossref PubMed Scopus (11) Google Scholar Similarly, in Gabonese school children, it was demonstrated that both the cellular and humoral responses to influenza and tetanus vaccines were lower among children in rural settings compared with those in semi-urban settings.8van Riet E Adegnika AA Retra K et al.Cellular and humoral responses to influenza in Gabonese children living in rural and semi-urban areas.J Infect Dis. 2007; 196: 1671-1678Crossref PubMed Scopus (58) Google Scholar, 9van Riet E Retra K Adegnika AA et al.Cellular and humoral responses to tetanus vaccination in Gabonese children.Vaccine. 2008; 26: 3690-3695Crossref PubMed Scopus (33) Google Scholar The lower efficacy and impaired immune response in the rural group in the study by Choi and colleagues2Choi EM-L Lacarra B Afolabi MO et al.Safety and immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in infants: a phase 2, randomised, double-blind, active-controlled trial in Guinea and Sierra Leone.Lancet Glob Health. 2023; 11: e1743-e1752Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar support these findings and warrant further investigation into the modulating factors. Such a study on the variation of immune response among infants in rural and urban settings will be crucial for public health interventions as Ebola outbreaks tend to start from rural areas and move to populated urban centres.10Okware SI Omaswa F Talisuna A et al.Managing Ebola from rural to urban slum settings: experiences from Uganda.Afr Health Sci. 2015; 15: 312-321Crossref PubMed Scopus (28) Google Scholar The study by Choi and colleagues2Choi EM-L Lacarra B Afolabi MO et al.Safety and immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in infants: a phase 2, randomised, double-blind, active-controlled trial in Guinea and Sierra Leone.Lancet Glob Health. 2023; 11: e1743-e1752Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar aligns with the current research practice focusing on candidate vaccines for pathogens of potential epidemics. The first point of alignment is to design clinical trials on the safety and immunogenicity of vaccine candidates that target future outbreaks. Trials on safety and immunogenicity are done as a proxy for vaccine efficacy studies since they are used in preparation for future outbreaks. This was shown in the PREVAIL 1 Ebola vaccine trial conducted in Liberia,6Kennedy SB Bolay F Kieh M et al.Phase 2 placebo-controlled trial of two vaccines to prevent Ebola in Liberia.N Engl J Med. 2017; 377: 1438-1447Crossref PubMed Scopus (168) Google Scholar wherein the data on the safety and immunogenicity of the candidate vaccine supported a larger vaccine trial in Guinea.11Henao-Restrepo AM Camacho A Longini IM et al.Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Suffit!).Lancet. 2017; 389: 505-518Summary Full Text Full Text PDF PubMed Scopus (679) Google Scholar The second point of alignment is in the use of existing vaccine safety and immunogenicity data from previous studies to conduct studies among infants younger than 1 year. We have seen this use of previous data in the PREVAC trial,12PREVAC Study TeamRandomized trial of vaccines for Zaire Ebola virus disease.N Engl J Med. 2022; 387: 2411-2424Crossref PubMed Scopus (9) Google Scholar which used data from adult studies to target children younger than 18 years—ie, the vaccine trial was first designed for adults and excluded the most vulnerable groups (eg, infants, women who are pregnant, and lactating mothers). Based on the safety and immunogenicity findings of the study, other groups can be gradually included through dosing to create more substantial vaccine coverage in the event of an actual outbreak.12PREVAC Study TeamRandomized trial of vaccines for Zaire Ebola virus disease.N Engl J Med. 2022; 387: 2411-2424Crossref PubMed Scopus (9) Google Scholar From a critical review of this paper, we do know that during Ebola virus and other major infectious disease outbreaks, the entire population can be at risk. However, the most vulnerable groups, such as infants, are often not protected by vaccines as clinical trials exclude them due to their increased vulnerability and other ethical issues that could further amplify the concerns of the growing anti-vaccine communities. Choi and colleagues2Choi EM-L Lacarra B Afolabi MO et al.Safety and immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in infants: a phase 2, randomised, double-blind, active-controlled trial in Guinea and Sierra Leone.Lancet Glob Health. 2023; 11: e1743-e1752Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar show an ethical way to design a vaccine trial based on data on children and expand it to infants. However, the trial required intensive and strategic social mobilisation and community engagement with parents to build trust and to ensure clinical benefits for the control groups. Furthermore, future studies assessing the disparities in immune responses in rural and urban settings will inform the design of public health interventions during outbreaks. The key takeaway is that the study has demonstrated that infants can safely have access to the Ebola vaccines, just like adults, in the event of the next Ebola outbreak. This online publication has been corrected. The corrected version first appeared at thelancet.com/lancetgh on October 31, 2023 This online publication has been corrected. The corrected version first appeared at thelancet.com/lancetgh on October 31, 2023 We declare no competing interests. Safety and immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in infants: a phase 2, randomised, double-blind, active-controlled trial in Guinea and Sierra LeoneAd26.ZEBOV and MVA-BN-Filo was well tolerated and induced strong humoral responses in infants younger than 1 year. There were no safety concerns related to vaccination. Full-Text PDF Open AccessCorrection to Lancet Glob Health 2023; 11: e1672–73Fallah MP, Gonese E, Sembuche S, Ndembi N. Infants can access Ebola vaccines during outbreaks. Lancet Glob Health 2023; 11: e1672–73—In this Comment, the title was updated to correct a grammatical error. This correction has been made as of Oct 31, 2023. Full-Text PDF Open Access